Synthesis of 4- and 4,5-functionalized imidazol-2-ylidenes from a single 4,5-unsubstituted imidazol-2-ylidene

Article abstract of DOI:10.1021/ja102639a

Using the nucleophilicity of NHCs and a NHCs, as well as the leaving group ability of the former, the carbon-carbon double bond of imidazol-2-ylidenes can be readily mono- and difunctionalized. These results provide also a new light on the formation of abnormal carbene adducts from classical unsaturated NHCs.

Full text of DOI:10.1021/ja102639a

Published on Web 05/05/2010
Synthesis of 4- and 4,5-Functionalized Imidazol-2-ylidenes from a Single
4,5-Unsubstituted Imidazol-2-ylidene
Daniel Mendoza-Espinosa, Bruno Donnadieu, and Guy Bertrand*
UCR-CNRS Joint Research Chemistry Laboratory (UMR 2282), Department of Chemistry, UniVersity of California,
RiVerside, California 92521-0403
Received March 29, 2010; E-mail: guy.bertrand@ucr.edu
Since the discovery by Arduengo et al. of the stable 1,3-
diadamantyl imidazol-2-ylidene (1, R ) Ad),1,2 a myriad of the
so-called unsaturated N-heterocyclic carbenes (NHCs) have been
prepared, and numerous applications have been found.3 Because
of the commonly practiced synthetic routes, most unsaturated NHCs
feature an unsubstituted carbon-carbon double bond or alternatively
alkyl or aryl groups are placed at the 4 and 5 positions.4 The rare
exceptions are imidazol-2-ylidenes annulated to a quinone derivative
(A)5 or a heterocycle (such as B and C),6 the oxazoline derivatives
(D, E),7 and NHCs featuring one (F, G)8 or two (H)9 heavier main
group elements (Figure 1).
rearrangement of 1 is very unlikely since it is well established that
the isomeric aNHC is ∼70-80 kJ mol-1 higher in energy,
corresponding to a pKa value for the C5- proton (∼33) 9 units higher
than that for the C2 proton in the parent imidazolium salt;13
moreover, a 1,3-hydrogen shift would certainly be energetically
costly.14 Therefore, it is clear that the formation of aNHCs can
only be favored if the C2-position is protected, and indeed we have
recently shown that aNHC 2 can be prepared and even isolated
(Scheme 1, bottom).15
Scheme 1
Figure 1. Imidazol-2-ylidenes 1 and its derivatives A-H featuring C4
and/or C5 substituents different from H, alkyl, and aryl groups.
With the aim of tuning the electronic properties of aNHCs, we
chose to vary the C2-substituent, using NHC 1 (Ar ) Dipp) as a
starting material. Addition of 1 equiv of benzoyl chloride to 1
cleanly afforded the corresponding adduct 3a. However, deproto-
nation of 3a with potassium hexamethyldisilazide at -78 °C did
not lead to the expected aNHC 2a but to its isomeric NHC 4a,
which was isolated in 64% yield (Scheme 2). Its structure was
determined unambiguously by single crystal X-ray diffraction
(Figure 2). A plausible mechanism to rationalize these results
Interestingly, it has been shown that the substituents at the
carbon-carbon double bond have a dramatic influence on the elec-
tronic properties of the carbene center. For example, the dichlori-
nated derivatives H are exceptionally stable and are certainly the
only carbenes that can be handled in air.9a Therefore, practical
synthetic strategies, allowing the access to symmetrically and
unsymmetrically 4- and 4,5-functionalized imidazol-2-ylidenes, are
highly desirable. Herein we report a convenient route to a variety
of these compounds from a single precursor, namely a 4,5-
unsubstituted imidazol-2-ylidene of type 1 (Ar ) 2,6-diisoprop-
ylphenyl, Dipp).10 In addition, the mechanism of formation of the
so-called abnormal carbene adducts is discussed.
Scheme 2
The syntheses of NHCs A-E follow classical methods, using
precursors already featuring the desired backbone. In contrast, NHCs
F-H are obtained in a single operation from the corresponding
4,5-unsubstituted NHCs of type 1. The latter results are reminiscent
of the discovery by Crabtree that 2-pyridylmethylimidazolium salts
react with IrH5(PPh3)2 to give a complex in which the imidazole
ring bound the “wrong way” at C5 and not at C2 (Scheme 1, top).11
The mechanism of formation of C5-bound adducts is still obscure,
whether a transition metal is involved or a main group element as
in F-H.12 These adducts correspond to a formal rearrangement of
imidazol-2-ylidene 1 into its isomeric C5-deprotonated imidazolium,
a so-called abnormal carbene (aNHC), followed by addition of
the electrophile, and finally deprotonation at C-2. However, the
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7264 J. AM. CHEM. SOC. 2010, 132, 7264–7265
10.1021/ja102639a  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 4
romethane sulfonyl, which should decrease the σ-donor and increase
the π-acceptor ability of NHCs. Moreover, these results provide a
new light on the formation of abnormal carbene adducts from
classical unsaturated NHCs.
Figure 2. Molecular structures of 4a (left) and 4f (right) in the solid state
(hydrogen atoms are omitted for clarity; ellipsoids are drawn at 50%
probability). Selected bond lengths [Å] and angles [deg]; 4a: N1-C2
1.372(8), N3-C2 1.351(8), N3-C4 1.389(8), N1-C5 1.380(8), C4-C5
1.366(10), C4-C6 1.464(9), C6-O1 1.229(7), N1-C2-N3 101.9(5), 4f:
N3-C2 1.3695(15), N1-C2 1.3714(15), N1-C5 1.3848(15), N3-C4
1.4071(14), C4-C5 1.3510(17), C4-P1 1.8124(12), N3-C2-N1 101.31(9).
Acknowledgment. We are grateful to the NIH (R01 GM 68825)
and DOE (DE-FG02-09ER16069) for financial support.
Supporting Information Available: Full experimental details; X-ray
crystallographic data for 4a and 4f in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
involves the deprotonation of 3a with formation of aNHC 2a as a
fleeting intermediate. The latter then acts as a nucleophile toward
3a, generating the bis-adduct 5a along with 1. NHC 1 can act as a
nucleophile toward the former leading to the observed 4-substituted
NHC 4a and regenerating the starting material 3a. To confirm the
viability of this hypothesis, stable aNHC 2 was added to the
2-benzoyl imidazolium 3a, and indeed the formation of the penta-
substituted imidazolium salt 5b was observed along with NHC 1.
Then, imidazolium salt 5a, prepared by addition of benzoyl chloride
to 4a, was reacted with 1, which led to C5-substituted imidazol-
2-ylidene 4a and C2-substituted imidazol-2-ylidene 3a.
The scope of this reaction is quite general as shown in Scheme
3. A variety of C4-functionalized NHCs 4a-f were prepared in
moderate to good isolated yields (not optimized). Of special interest,
both electron-withdrawing and -donating groups can be used to
functionalize the carbon-carbon double bond of NHCs.
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Scheme 3
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When combined with the recent discovery of modular syntheses
of N,N′-unsymmetrically substituted imidazolium salts,4 these
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any substitution pattern. Particularly appealing is the possibility of
placing strong electron-withdrawing groups, such as trifluo-
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